Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

BACKGROUND: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. OBSERVATIONS: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. CONCLUSIONS AND RELEVANCE: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.

Hematopoietic Stem Cell Transplantation in Sickle Cell Disease: A Multidimentional Review.

While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first cell-based gene therapies for the treatment of patients 12 years of age and older with sickle cell disease (SCD), this treatment is not universally accessible. Allogeneic hematopoietic stem cell transplant (HSCT) has the potential to eradicate the symptoms of patients with SCD, but a significant obstacle in HSCT for SCD is the availability of suitable donors, particularly human leukocyte antigen (HLA)-matched related donors. Furthermore, individuals with SCD face an elevated risk of complications during stem cell transplantation due to SCD-related tissue damage, endothelial activation, and inflammation. Therefore, it is imperative to consider optimal conditioning regimens and investigate HSCT from alternative donors. This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and posttransplant outcomes.

Clinical Features and Risk Factors of Relapse and Mortality in Thrombotic Thrombocytopenic Purpura Patients: A Seven-Year Experience.

Background: Thrombotic thrombocytopenic purpura (TTP) is associated with microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. No comprehensive report exists on clinical characteristics and risk factors of relapse and mortality in Iranian TTP patients. In this study, we aimed to report clinical features of Iranian TTP patients, to evaluate disease relapse and mortality rate and their associated risk factors. Materials and Methods: This study was a cohort study of patients diagnosed with microangiopathic hemolytic anemia admitted to the Shariati Hospital, Tehran, a referral center for TTP patients, from 2010 to 2017. Demographic, clinical, and laboratory data were recorded and patients were followed for 3 years regarding disease relapse and mortality. Results:  114 patients (80 females, 34 males) with a mean age of 39.3 ± 14.99 years were included.  Hematologic and neurologic symptoms were the most common manifestations. Abnormal laboratory findings at the presentation included thrombocytopenia, anemia, and elevated LDH. All patients were treated with plasma exchange, and 75.5% of them had a response to treatment, while the 3-year relapse and mortality rate was 23.6 and 26.3%.  Lower platelet count was a predictor of disease relapse. Age, hematological, or neurological initial presentation were associated with TTP mortality. Conclusion: Based on the largest study of TTP patients ever in Iran, the demographic and clinical characteristics of Iranian TTP patients are similar to other existing reports. Knowledge of the risk factors for TTP relapse and mortality could be useful to alert hematologists for prompt therapeutic actions when necessary.

Incidence of hemorrhagic cystitis following unmanipulated peripheral blood stem cell transplantation in acute Leukemia: A retrospective single-center risk factor analysis.

BACKGROUND: Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality. OBJECTIVES: In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors. STUDY DESIGN: We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models. RESULTS: A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR = 4.88; 95%CI: (1.51-15.78), P = 0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR = 6.36; 95%CI: (1.58-25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83-17.75), P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P < 0.001). DISCUSSION: Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group. CONCLUSIONS: Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC.

Offshore detention: cross-sectional analysis of the health of children and young people seeking asylum in Australia.

OBJECTIVE: To describe the health and well-being of children and young people (CYP) seeking asylum subjected to Australia's immigration policy of indefinite mandatory detention on Nauru. DESIGN: Cross-sectional analysis of a cohort of CYP seeking asylum. SETTING: Australian paediatric clinicians from 10 health services completed detailed health assessments around the time of transfer from Nauru, mostly to Australia. PARTICIPANTS: Sixty-two CYP who were ≤18 years on entry into offshore immigration detention on Nauru between 2013 and 2019. Mean age at health assessment was 9 years. MAIN MEASURES: Health outcomes were categorised as physical, mental or neurodevelopmental concerns/conditions. Risk and protective factor data were collected using the adverse childhood experiences and refugee-specific adverse childhood experiences tools. RESULTS: Over half of the CYP (n=32, 52%) were held on Nauru for ≥4 years. The vast majority of CYP had physical health (n=55, 89%) and mental health (n=49, 79%) concerns including self-harm or suicidal ideation/attempt (n=28, 45%). Mental health concerns were more likely in CYP who were school-aged (p=0.001), had been held on Nauru for ≥1 year (p=0.01); originated from the Eastern Mediterranean region (p<0.05); witnessed trauma (p<0.05) or had exposure to ≥4 refugee-specific adverse childhood experiences (p<0.05). Neurodevelopmental concerns were seen in eight children (13%). CONCLUSIONS: This study highlights the almost universal physical and mental health difficulties in a sample of CYP who experienced forced migration and were subjected to Australia's offshore immigration detention policy. Immigration detention in recipient countries, a known adverse childhood experience, may contribute to or exacerbate harmful outcomes in CYP seeking asylum.

Regional cerebral blood flow and brain atrophy in mild cognitive impairment and Alzheimer's disease.

Objectives: A decline in the regional cerebral blood flow (CBF) is proposed to be one of the initial changes in the Alzheimer's disease process. To date, there are limited data on the correlation between CBF decline and gray matter atrophy in mild cognitive impairment (MCI) and AD patients. to investigate the association between CBF with the gray matter structural parameters such as cortical volume, surface area, and thickness in AD, MCI, and healthy controls (HC). Methods: Data from three groups of participants including 39 HC, 82 MCI, and 28 AD subjects were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI). One-way ANOVA and linear regression were used to compare data and find a correlation between structural parameters such as cortical volume, surface area, and thickness and CBF which measured by arterial spin labeling (ASL)-MRI. Results: Our findings revealed a widespread significant correlation between the CBF and structural parameters in temporal, frontal, parietal, occipital, precentral gyrus, pericalcarine cortex, entorhinal cortex, supramarginal gyrus, fusiform, precuneus, and pallidum. Conclusion: CBF decline may be a useful biomarker for MCI and AD and accurately reflect the structural changes related to AD. According to the present results, CBF decline, as measured by ASL-MRI, is correlated with lower measures of structural parameters in AD responsible regions. It means that CBF decline may reflect AD-associated atrophy across disease progression and is also used as an early biomarker for AD and MCI diagnosis.

Metformin use and brain atrophy in nondemented elderly individuals with diabetes.

OBJECTIVE: There is a shred of growing evidence demonstrating that diabetic patients are at higher risk of developing Alzheimer's disease compared to the general population. The previous investigation showed the protective effect of metformin for delaying dementia in diabetic patients. However, there are limited data on the effect of metformin on structural changes. This study aims to investigate the effect of metformin on hippocampal and cortical volumes in non-demented diabetic individuals. METHOD: We entered 157 non-demented diabetic subjects including 89 mild cognitive impairment (MCI), and 68 cognitively healthy individuals from Alzheimer's disease Neuroimaging Initiative (ADNI) which were then categorized as metformin users and non-users. We used the ANCOVA model for measuring the association between metformin use and hippocampal and cortical volumes. RESULTS: Among 157 subjects with a mean age of 71.8 (±7.7) included in this study, 76 individuals were stratified as metformin users. Results of the univariate model indicate that metformin users had a higher right (p = 0.003) and left parietal lobe volume (p = 0.004). Moreover, the volume of left cingulate was higher in those who used metformin compared to those not used it (p = 0.027). Our results were also significant for the right frontal lobe and indicated that metformin users had higher volume (p = 0.035). There were no significant differences in the hippocampus, occipital, and temporal regions. CONCLUSION: Our findings showed the protective effects of metformin on brain volumes in non-demented elderly individuals with diabetes. Comparing the groups show strong enough results regarding the lower atrophy in metformin users.

Plasma p-tau181 associated with structural changes in mild cognitive impairment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dementia and is a serious concern for the health of individuals and government health care systems worldwide. Gray matter atrophy and white matter damage are major contributors to cognitive deficits in AD patients, as demonstrated by magnetic resonance imaging (MRI). Many of these brain changes associated with AD begin to occur about 15 years before the onset of initial clinical symptoms. Therefore, it is critical to find biomarkers reflective of these brain changes associated with AD to identify this disease and monitor its prognosis and development. The increased plasma level of hyperphosphorylated tau 181 (p-tau181) has been recently considered a novel biomarker for the diagnosis of AD, preclinical AD, and mild cognitive impairment (MCI). In the current study, we examined the association of cerebrospinal fluid (CSF) and plasma levels of p-tau181 with structural brain changes in cortical thickness, cortical volume, surface area, and subcortical volume in MCI patients. In this cross-sectional study, we included the information of 461 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The results of voxel-wise partial correlation analyses showed a significant negative correlation between the increased levels of plasma p-tau181, CSF total tau, and CSF p-tau181 with structural changes in widespread brain regions. These results provide evidence for the use of plasma p-tau181 as a diagnostic marker for structural changes in the brain associated with the early stages of AD and neurodegeneration.

Autoimmune encephalitis associated with COVID-19: A systematic review.

INTRODUCTION: There are increasing reports of COVID-19 related neurological complications which may be due to direct viral invasion, or immune mediated inflammatory diseases such as autoimmune encephalitis and ADEM (acute demyelinating encephalomyelitis). In this study, a systematic review is presented of the reported cases infected by the COVID-19 who were diagnosed with various forms of autoimmune encephalitis (AE). METHODS: The authors searched three databases including PubMed, Scopus, and Web of science for extracting original articles on coronavirus/ COVID-19 and AE. RESULTS: Eighteen articles were considered in this study, including 15 case reports, and three case series with a total of 81 patients. Among the studies, 19 cases were reported with AE including 7 (37%) cases of limbic encephalitis, 5 (26%) patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 2 (11%) with AE presenting as new-onset refractory status epilepticus (NORSE), 1 (5%) case of steroid-responsive encephalitis, and 4 (21%) cases with an unknown type of AE. CONCLUSION: Our systematic review revealed evidence on AE development in patients infected with the COVID-19. Clinicians should be aware of the possible diagnosis of AE when considering other neurological differential diagnosis in SARS-CoV-2 infected patients.

Plasma neurofilament light levels correlate with white matter damage prior to Alzheimer's disease: results from ADNI.

BACKGROUND: The blood biomarker neurofilament light (NFL) is one of the most widely used for monitoring Alzheimer's disease (AD). According to recent research, a higher NFL plasma level has a substantial predictive value for cognitive deterioration in AD patients. Diffusion tensor imaging (DTI) is an MRI-based approach for detecting neurodegeneration, white matter (WM) disruption, and synaptic damage. There have been few studies on the relationship between plasma NFL and WM microstructure integrity. AIMS: The goal of the current study is to assess the associations between plasma levels of NFL, CSF total tau, phosphorylated tau181 (P-tau181), and amyloid-ß (Aß) with WM microstructural alterations. METHODS: We herein have investigated the cross-sectional association between plasma levels of NFL and WM microstructural alterations as evaluated by DTI in 92 patients with mild cognitive impairment (MCI) provided by Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. We analyzed the potential association between plasma NFL levels and radial diffusivity (RD), axial diffusivity (AxD), mean diffusivity (MD), and fractional anisotropy (FA) in each region of the Montreal Neurological Institute and Hospital (MNI) atlas, using simple linear regression models stratified by age, sex, and APOE ε4 genotype. RESULTS: Our findings demonstrated a significant association between plasma NFL levels and disrupted WM microstructure across the brain. In distinct areas, plasma NFL has a negative association with FA in the fornix, fronto-occipital fasciculus, corpus callosum, uncinate fasciculus, internal capsule, and corona radiata and a positive association with RD, AxD, and MD values in sagittal stratum, corpus callosum, fronto-occipital fasciculus, corona radiata, internal capsule, thalamic radiation, hippocampal cingulum, fornix, and cingulum. Lower FA and higher RD, AxD, and MD values are related to demyelination and degeneration in WM. CONCLUSION: Our findings revealed that the level of NFL in the blood is linked to WM alterations in MCI patients. Plasma NFL has the potential to be a biomarker for microstructural alterations. However, further longitudinal studies are necessary to validate the predictive role of plasma NFL in cognitive decline.

Association of cognitive impairment and quality of life in patients with multiple sclerosis: A cross-sectional study.

Background: Cognitive impairments in patients with multiple sclerosis (MS) are suggested as a prognostic factor for disease development, and consequently higher disability and more deficits in daily and social activities. In this regard, we aimed to investigate the association between quality of life (QOL) and cognitive function in patients with MS. Methods: We conducted a cross-sectional study on patients with relapsing-remitting MS (RRMS). General characteristic variables were carried out, and then all patients underwent assessments such as Multiple Sclerosis Quality of Life-54 (MSQOL-54), Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS), Expanded Disability Status Scale (EDSS), Beck Depression Inventory-II (BDI-II), and North American Adult Reading Test (NAART). Results: In the present study, a total of 92 patients, including 76 women with a mean disease duration of 6.82 ± 4.80 years were involved. Results of simple Pearson correlation revealed a significant positive relation between California Verbal Learning Test (CVLT) total learning with MSQOL mental health (r = 0.267, P = 0.017) and physical health (r = 0.299, P = 0.007). After adjusting for potential confounders, there was a negative correlation between MSQOL mental health with Delis-Kaplan Executive Function System (D-KEFS) (r = -0.303, P = 0.015) and Judgment of Line Orientation (JLO) (r = -0.310, P = 0.013). Besides, MSQOL physical health was negatively associated with Brief Visuospatial Memory Test-Revised (BVMT-R) in the adjusted model (r = -0.270, P = 0.031). Conclusion: There is a statistically significant association between specific aspects of cognitive decline and QOL. Therefore, more attention should be paid to cognitive impairment in patients with MS as based on our findings, it is significantly associated with QOL.

Statins and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a paralytic, heterogeneous and progressive disease characterized by the degeneration of both upper and lower motor neurons. Several studies about the effects of statins drug on the risk of ALS showed contradictory results and evidence for this is inconclusive. So we aimed to perform a meta-analysis on previous studies to clarify the association between statin use and risk of ALS. The databases including PubMed, Scopus, and Web of science were searched in February 2021 for studies that reported the association between statin use and risk of ALS. The eligible studies had to provide a report on the effect of statin and the incidence of ALS while comparing it to the control group. Articles that had low statin exposure time, the absence of a control group and an unknown number of ALS patients were excluded. The rate ratio and 95% confidence interval (CI) were used for association measures in case-control and cohort studies. After full-text and abstract review, data from 8 studies with a total of 547,622 participants and 13,890 cases of ALS were entered in the present meta-analysis. We combined eight studies using a random-effect model and the RR for statin users among groups was 0.98 (95% CI 0.80-1.20) which indicates no association between statin and incidence of ALS. Also high heterogeneity was detected across the studies (Q value = 26.62, P = .00; I2 = 72.71%). In our meta-analysis study, we found no association between statin use and an increase in ALS incidence. This result is in line with some previous studies and provides strong evidence that denies the possible association between statin uptake and disease induction.

Zinc-salt assisted synthesis of three-dimensional oxygen and nitrogen co-doped hierarchical micro-meso porous carbon foam for supercapacitors.

Nitrogen and oxygen co-doped hierarchical micro-mesoporous carbon foams has been synthesized by pyrolyzation treatment of a preliminary foam containing melamine and formaldehyde as nitrogen, carbon and oxygen precursors and Zn(NO3)2. 6H2O and pluronic F127 as micro-meso pores generators. Several characterizations including thermal gravimetric analysis (TGA), X-ray diffraction (XRD) and Raman spectroscopy, FTIR and X-ray photoelectron spectroscopy, N2 adsorption-desorption, field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) were performed on the prepared foams. X-ray diffraction patterns, Raman spectra and N2 adsorption-desorption results confirmed that ZnO has pronounced effect on the graphitization of the prepared carbon foam. From X-ray diffraction, thermal gravimetric and N2 adsorption-desorption analysis results it was confirmed that the carbothermal reaction and the elimination of ZnO and also the elimination of pluronic F127 are the main factors for the induction of porosities in the foam structure. The presence of Zn(NO3)2. 6H2O and pluronic F127 in the initial composition of the preliminary foam results in the specific surface area as high as 1176 m2.g-1 and pore volume of 0.68 cm3.g-1. X-ray photoelectron and FTIR spectroscopy analyses results approved the presence of nitrogen (about 1.9 at %) in the form of pyridinic, graphitic and nitrogen oxide and oxygen (about 7.5 at. %) functional groups on the surface of the synthesized carbon foam. Electrochemistry analysis results including cyclic voltammetry (CV) and galvanostatic charge-discharge (GCD) and also electrochemical impedance spectroscopy (EIS) analysis illustrated the formation of an electric double layer supercapacitor with the capacitance as high as 137 Fg-1.